Journal Article

Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation

Rizzi, Marta, Janda, Ales, Zelinski, Teresa, Wirth, Thomas, Ehl, Stephan, Rosenberg, Alan, Borte, Stephan, Schwarz, Klaus, Pannicke, Ulrich, Holzmann, Karlheinz, Rump, Eva-Maria, Hese, Katrin, Schlesier, Michael, Schrezenmeier, Hubert, Schroeder, Marlis L, Baumann, Bernd, Laux, Constanze, Henneke, Philipp, Rensing-Ehl, Anne, Fuchs, Sebastian

2013

Overview

A subset of patients with severe combined immunodeficiency have nearly normal numbers of B and T cells that do not work. This study shows that an inability to phosphorylate IκB prevents cell activation and leads to defective immunity. Severe combined immunodeficiency (SCID) is the most severe primary immunodeficiency. Affected infants usually present in the first months of life with Pneumocystis jirovecii pneumonia, bacterial sepsis, chronic cytomegalovirus or candida infection, or persistent respiratory or gastrointestinal viral infection, often associated with protracted diarrhea and failure to thrive. 1 Impaired T-cell immunity is the main immunologic abnormality in SCID, and most patients have low numbers of T cells or none. However, some patients may have normal T-cell counts with a severe immune-cell activation defect. 2 Immune-cell activation involves complex signaling that regulates transcriptional programs. The nuclear factor κB (NF-κB) transcription factors are key . . .

• Publisher: Massachusetts Medical Society
• Subject: Adaptive Immunity - genetics / Agammaglobulinemia / Agammaglobulinemia - genetics / Airway management / B-Lymphocytes - physiology / Biological and medical sciences / Cell activation / Cell-mediated immunity / Chromosome 8 / Cytokine receptors / Embryos / Fatal Outcome / Female / Gene mapping / General aspects / Genes, Recessive / Humans / Humoral immunity / Hypogammaglobulinemia / I-kappa B Kinase - deficiency / I-kappa B Kinase - genetics / IKK protein / IKK2 protein / Immune system / Immunity, Innate - genetics / Immunology / Immunoregulation / Indians, North American / Infant / Infant, Newborn / Inflammation / Innate immunity / Kinases / Lymphocyte Activation / Lymphocyte Count / Lymphocytes B / Lymphocytes T / Male / Medical research / Medical sciences / Mitogens / Mutation / NF-κB protein / Pedigree / Peripheral blood / Phenotypes / Sequence Analysis, DNA / Severe combined immunodeficiency / Severe Combined Immunodeficiency - genetics / Signal transduction / T-Lymphocytes - physiology / Toll-like receptors / Transcription factors